Method of preparing orthohalomercuriphenol



Patented Mar. 28, 1950 UNITED STATES PATENT OFFICE METHQID F PREKARING ORTHO- HALOMERCURIPHENOL No Drawing. Application September 21, 1945, Serial No. 617,924

18 Claims.

This invention relates to the preparation of ortho-halomercuriphenols, particularly orthochloromercuriphenol, and is especially concerned with a novel method for preparing the aforesaid compounds wherein outstanding advantages are achieved in relation to simplicity of operation, saving in time, increase in yield, and concomitant reduction in cost of preparation.

Ortho-chloromercuriphenol, while one of the most powerful bacteriostatic agents of numerous common mercurial compounds heretofore studied, has had only limited use primarily because previously known methods for its production have been cumbersome to operate, have produced relatively low yields, and, as a result, said compound was obtainable only at comparatively high prices.

Thus, for example, although several methods have heretofore been proposed for preparing ortho-chloromercuriphenol, perhaps the most effective has been that described in Organic Syntheses, Collective Volume I, at page 155. In the said method, phenol at 170 degrees C. is treated gradually with mercuric acetate and the mercuration product is poured into hot water, the resulting suspension is boiled and is then filtered from the tars or tarry materials produced in the reaction. Then, sodium chloride is added to the filtrate to precipitate the para-isomer, namely, para-chloromercuripheno1, and the latter is filtered out from the hot solution. The cooled filtrate deposits ortho-chloromercuriphenol which is collected by filtration. The yield of orthochloromercuriphenol is stated to be 44%. However, when the method is carried out on a commercial scale, using substantial quantities of reactants, the yield of ortho-chloromercuriphenol is usually of the order of about to of the theoretical based on the quantity of mercuric acetate employed. v

There are numerous disadvantages and objections to the above described method which, in the practice of our invention, as hereafter described in detail, are overcome. Thus, for example, the known method is hazardous to operate in that, with reaction temperatures of the. order of 170 degrees 0., possible phenol burns are a serious menace. Such high temperatures are required, in accordance with the aforesaid method, in order to produce even the previously stated yields of ortho-chloromercuriphenol, such elevated temperatures favoring an increase in the proportion of the ortho derivative at the expense of the relatively undesired para derivative. As a result of the necessity for operating under such elevated temperatures, substantial quantities of tarry materials are formed which, among other things, introduce serious difiiculties in filtration.

In accordance with our present invention, ortho-halomercuriphenols, particularly exemplifled by ortho-chl.oromcrcuriphenol, are produced by a method having marked advantages over heretofore known procedures. In the first place, our method may be carried out at relativel low temperatures, for example, temperatures up to about 95 degrees and preferably within the range of degrees C. degrees 0., a particularly preferred range being approximately 88 degrees C.93 degrees C. This relatively low temperature of operation makes it possible to carr out the initial mercuration reaction using ordinary steam-heated kettles or conventional Pfaudler equipment, rather than special equipment such as gas-fired or Dowtherm heated reaction vessels. In addition, the tarry materials, formed in relatively substantial quantities in the aforementioned known method, are non-existent in the method of our present invention, thereby speeding up materially the production of ortho-chloromercuriphenol by virtue of the elimination of filtration and purification problems. Still further, in the practice of our method, yields of ortho-chloromercuriphenol are readily obtained, on a commercial scale, of the order of 65% of the theoretical, based on the amount of mercuric acetate employed, such yields representing, in general, approximately twice those which are usually obtained in accordance with the aforementioned known method. Finally, mercuric oxide and acetic acid ma be utilized in place of the more expensive mercuric acetate, the mercuric oxide being converted into mercuric acetate in situ in our method. The utilization of mercuric oxide in the Organic Syntheses method, for example, would, from a practical standpoint, be virtually impossible in that the addition of a mixture of mercuric oxide containing excess acetic acid to phenol at a temperature approximately degrees 0. would be exceedingly hazardous.

In accordance With our present invention, the important improvements which have been outlined above are obtained by carrying out the mercuration reaction with the phenol in the presence of fluorides of hydrogen, boron and antimony as, for example, aqueous or anhydrous hydrofluoric acid, boron trifluoride and antimony trifiuoridc. Instead of using the aforesaid fluorides as such, or in the form of a solution thereof or the like, any agents which will form or liberate any of the aforesaid fluorides in the reaction mixture may be utilized and, wherever reference is made in the claims to the aforesaid fluorides, it will be understood to encompass such materials. Boron trifluoride is unusually satisfactory. The proportions of the aforesaid fluorides which may be utilized are subject to considerable variation but good results are, in general, obtained by employing from about 1% to about based on the weight of the total reactants. While materially greater proportions of said fluorides may be employed, particularly in the case of anhydrous hydrofluoric acid, their use is ordinarily not of sufficient advantage to be warranted.

After the mercuration reaction has been completed, the reaction mixture is then treated to convert the phenol mercuric compounds to the halo derivatives. This is conveniently done by pouring the reaction mixture into hot water, preferably boiling the resulting suspension for a few minutes, filtering, adding an alkali metal halide to precipitate out the parahalomercuriphenol, removing the latter by filtration, and then recovering the desired ortho-halomercuriphenol by crystallization from the cooled filtrate. Where ortho-chloromercuriphenol is to be produced, the alkali metal halide which we prefer to employ is sodium chloride or common salt. Where the ortho-halomercuriphenol to be produced is the bromo-, iodo-, or fluoro-derivatlve, sodium bromide, sodium iodide, or sodium fiuoride, as the case may be, may be utilized.

In order that those skilled in the art may more fully understand the nature of the present invention, the following illustrative examples are set forth. It will be appreciated that the proportions of reacting ingredients, times of reaction, order of steps and temperatures may be varied, as indicated herein, and that supplementary processes of purification and the like may be resorted to wherever found desirable or convenient. These and other variations and m.odifi cations will be evident to those skilled in the art in the light of the guiding principles which are disclosed herein.

Example 1 28.2 g. (26.4 cc.) of phenol was placed in, a reaction flask, 4 cc. of boron trifluoride in glacial acetic acid (200 g. per liter) was added and the solution heated to approximately 88 degrees C. 31.9 g. of mercuric acetate was added to this solution over a period of 5 minutes. The reaction mixture was kept at approximately 96 degrees C. for hour. Thereafter, it was slowly poured into 860 cc. of water, which was previously heated to a temperature of approximately 23 degrees C. The resulting solution was boiled for 5 minutes and then filtered hot. 11 g. of solid sodium chloride was added to cause precipitation of para-chloromercuriphenol. Thelatter material was filtered from the hot solution and the resulting filtrate allowed to cool overnight. The ortho-chloromercuripheno1 crystallized from this filtrate and was obtained in a yield of 63.6% of the theoretical. The para isomer was obtained in a yield of approximately 1. of the theoretical.

Example 2 Thereupon, the mixture was poured into 'l-7 gallons of boiling water.

poured into 860 cc. of water at degrees C. The resulting hot solution was filtered and 11 g. of solid sodium chloride was added to the hot filtrate. By-product para-chloromercuriphenoi was removed by filtration of this hot mixture. The filtrate was cooled to room temperature and allowed to stand overnight. The orthochloro mercuriphenol was filtered 01f and was recovered in 55.2% ield. The para isomer was obtained in approximately 33% yield.

Example 3 845 cc. of glacial acetic acid was placed in a 5-liter three-necked flask fitted with thermometer and stirrer. 827 g. of yellow oxide of mercury was introduced and the mixture heated and stirred until most of the mercuric oxide had dissolved. 1013 cc. of phenol was added and the reaction mixture heated to 90 degrees C. Then 305 cc. of a glacial acetic acid solution of boron trifiuoride (containing 100 g. per liter) was added, the temperature of the reaction mixture being maintained for 10 to 15 minutes at about so degrees C. The reaction mixture was then The resulting solution was kept near the boiling point for 5 minutes. 418 g. of common salt was added and the mixture filtered hot to remove the precipitated para-chloromercuriphenol. The filtrate was allowed to cool overnight, and the precipitated orthochloromercuriphenol isolated. A yield-of 57.5% of the ortho isomer and 19% of the para isomer was obtained.

Concentration of the mother liquors and subsequent cooling produced an additional yield of about 6%. Thus, an overall yield of about 63.5% wasrealized of the orthochloromercuriphenol.

It is particularly desirable to carry out the mercuration reaction in an acetic acid solution particularly glacial acetic acid, since the aetic acid serves as a mutual solvent for the mercurating agent and the phenol. Other solvents, however, may be employed, although with less satisfaction, such solvents being disclosed, for example, in United States Patent No. 2,353,312.

As previously pointed out, it is particularly preferred to carry out the mercuration reaction at temperatures in the range of approximately 80 degrees C. degrees C. and especially in the range of about 88 degrees C.-93 degrees C. It possible, however, to carry out the reaction at materially lower temperatures but, in such cases, the reaction takes a somewhat longer period of time. It isalso possible to operate at materially higher temperatures than 95 degrees (2., but the full advantages of the invention are obtained when the relatively lower operating temperatures referred to above are utilized.

In general, for obtaining the best results, the phenol is employedin molal excess over that required to react with the mercur'ating agent to produce the phenol mercuric-compound. It is desirable, in general, that the phenol be present in the molal excess of about 2 to about '7 mols, particularly, about 3 to about 4 mols, for each mol of mercurati'ng agent. The acetic acid or the like is preferably present in proportions of a fraction to about 2 mols per mol of mercuric oxide or mercuric acetate.

While the full advantages or the invention will be obtained in at least most cases by carrying out the mercuration at ordinary atmospheric pressures, it will be understood that, within the broader aspects of the invention, the utilization of greater than atmospheric pressures and, for

that matter, sub-atmospheric pressures, is not precluded. In other words, by conducting the mercuration reaction in the presence of any one or a mixture of any two or more of the aforesaid fluorides, various advantages accrue even if other than ordinary atmospheric pressures are employed.

It will be understood that, wherever the term mercuration or equivalent terminology is employed in the present specification and claims, the reaction covered thereb is one wherein mercury is combined directly onto the aromatic nucleus of the phenol.

While the invention has been described in detail, it is to be understood. that the scope thereof is not to be limited other than as set forth in the claims.

What we claim as new and desire to protect by Letters Patent of the United States is:

1. In a method of producing ortho-chloromercuriphenol, wherein mercuric acetate is reacted with phenol, the step which comprises carrying out the mercuration reaction in the presence of, at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimony trifluoride.

2. In a method of producing ortho-chloromercuriphenol, wherein mercuric acetate is reacted with phenol, the step which comprises carrying out the mercuration reaction in the presence of boron trifluoride.

3. In a method of producing ortho-chloromercuriphenol, wherein mercuric acetate is reacted with a molal excess of phenol, the step which comprises carrying out the mercuration reaction at a temperature in the range of about 80 degrees C.-95 degrees C. and in the presence of boron trifluoride.

4. In a method of producing ortho-chloromercuriphenol, the steps which comprise reacting phenol and mercuric acetate in the presence of at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimon trifluoride, said reaction being carried out at a temperature within the range of approximately 80 degrees 0-95 degrees C.

5. In a method of producing ortho-chloromercuriphenol, the steps which comprise reacting mercuric acetate with a molal excess of phenol in the presence of boron trifluoride, said reaction being carried out at a temperature within the range of approximately 80 degrees C.-95 degrees C.

6. In a method for the preparation of orthochloromercuriphenol, the steps which comprise reacting a solution containing phenol, acetic acid, and the mercuric compound selected from the group consisting of mercuric acetate and mercuric oxide, in the presence of at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimon trifluoride, the phenol being in molal excess over said mercuric compound, said recation being carried out at a temperature within the range of approximately 80 degrees C..-95 degrees C., at atmospheric pressure, admixing the reaction mixture with hot water, filtering, adding salt to precipitate para-chloromercuriphenol, and recovering the ortho-chloromercuriphenol from the filtrate.

7. In a method of producing ortho-chloromercuriphenol, the steps which comprise admixing mercuric oxide with a solution containing phenol, acetic acid, and boron trifluoride, reacting the mixture at substantially atmospheric pressure and at elevated temperature but not exceeding approximately 95 degrees 0., adding the reaction mixture to hot water, filtering, adding salt to the hot filtrate, filtering off para-chloromercuriphenol, and recovering the ortho-chloromercuriphenol from the filtrate.

8. In a method of producing ortho-chloromercuriphenol the steps which comprise providing a mixture of phenol, acetic acid, mercuric oxide and at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimony trifluoride, and reacting the same to effect mercuration of the phenol.

9. In a method of producing ortho-chloromercuriphenol, the steps which comprise providing a mixture of phenol, acetic acid, mercuric oxide and at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimony trifluoride, and reacting the same at a temperature within the range of approximately degrees C.- degrees C. to effect mercuration of the phenol.

10. In a method of producing orthc-chloromercuriphenol, the steps which comprise providing a mixture of acetic acid, boron trifluoride, mercuric oxide, and a molal excess of phenol, and reacting the same at a temperature within the range of approximately 80 degrees C.-95 degrees C., at atmospheric pressure, to efiect mercuration of the phenol.

11. In a method of producing an ortho-halomercuriphenol, wherein a mercuric salt is reacted with phenol, the step which comprises carrying out the mercuration reaction in the presence of at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimony trifluoride.

12. In a method of producing an ortho-halomercuriphenol, wherein a mercuric salt is reacted with phenol, the step which comprises carrying out the mercuration reaction in the presence of boron trifluoride.

13. In a method of producing an ortho-halomercuriphenol, the steps which comprise reacting phenol and a mercuric salt, in the presence of a mutual solvent for the phenol and said mercuric salt, and in the presence of at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimony trifluoride, said mercuration reaction being carried out at a temperature within the range of approximately 80 degrees C.- 95 degrees C.

14. In a method for the preparation of an or tho-halomercuriphenol, the steps which comprise reacting a solution containing phenol, acetic acid, and a mercuric compound selected from the group consisting of mercuric acetate and mercuric oxide, in the presence of at least one fluoride selected from the group consisting of hydrogen fluoride, boron trifluoride and antimony trifluoride, the phenol being in molal excess over said mercuric compound, said reaction being carried out at a temperature within the range of approximately 80 degrees C.-95 degrees 0., at atmospheric pressure, admixing the reaction mixture with hot water, filtering, adding an alkali metal halide, and recovering the ortho-halo-mercuriphenol.

15. In a method of producing an ortho-halomercuriphenol, wherein a mercuric salt is reacted with phenol, the step which comprises carrying out the mercuration reaction in the presence of at least one fluoride of an element selected from the group consisting of hydrogen, boron and antimony.

16. In a method of producing an ortho-halomercuriphenol, the steps which comprise reacting phenol and a mercuric salt, in the presence of a mutual solvent for the phenol and said mercuric salt, and in the presence of at least one fluoride of an element selected from the group consisting of hydrogen, boron and antimony, said mercuration reaction being carried out at a temperature within the range, of approximately 80 degrees C. 95 degrees C.

1'7. In a method of producing ortho-chloromercuriphenol, wherein mercuric acetate is reacted with phenol, the step which comprises carrying out the mercuration reaction in the presence of at least one fluoride of an element selected from the group consisting of hydrogen, boron and antimony.

18. In a method of producing ortho-chloromercuriphenol, the steps which comprise reacting phenol and mercuric acetate in the presence of at least one fluoride of an element selected from the group consisting of hydrogen, boron and antimony, said reaction being carried out at a temperature within the range of approximately 80 degrees C.-95 degrees C.

JULIUS F. KAPLAN. CHARLES MELLICK.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,135,450 Larson Nov. 1, 1938 2,135,451 Loder Nov. 1, 1938 2,162,459 Loder June 13, 1939 2,353,312 Kobe July 11, 1944 OTHER REFERENCES Ruif, Ber. Deutsch. Chem. Ges. vol. 39, (1906) pages 1310 to 4327.

Simons Petroleum Refiner, vol. 22, July 1943, pp. 189 to 193.

Niewland et al., Jour. Am. Chem. Soc., vol. 52, 1018 to 24 (1930).

Ibid McKenna et al., v01. 59, 470 and 471 (1937).

Ibid Henne et al., vol. 59, p. 2434 to 2436 (1937).

Ibid Sowa et al., vol. 59, p. 1202 and 1203 (1937).

Whitmore Organic Syntheses, collective vol. I (1932) p. 155.

Finger et al., Trans. Ill. State Acad. Sci, pp. 89 to 91 (1936). 

1. IN A METHOD OF PRODUCING ORTHO-CHLOROMERCURIPHENOL, WHEREIN MERCURIC ACETATE IS REACTED WITH PHENOL, THE STEP WHICH COMPRISES CARRYING OUT THE MERCURATION REACTION IN THE PRESENCE OF AT LEAST ONE FLUORIDE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN FLUORIDE, BORON TRIFLUORIDE AND ANTIMONY TRIFLUORIDE. 